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Protein Name Accession Number Molecular Weight Myovi-GTD

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MyoVI-GTD MyoVI-GTD MyoVa-MGT MyoVa-MGT Molecular Spectral Unique Spectral Unique Protein Name Accession Number Weight Counts Peptides Counts Peptides Dync1h1 Cytoplasmic dynein 1 heavy chain 1 IPI00119876 532 kDa 310 121 515 182 Spna2 Spectrin alpha 2 IPI00757353 285 kDa 853 170 597 149 Myo5a 215 kDa protein IPI00875222 215 kDa 162 47 874 109 AU042671 hypothetical protein LOC269700 isoform 1 IPI00762814 453 kDa 2 2 231 104 Spnb2 Isoform 1 of Spectrin beta chain, brain 1 IPI00319830 274 kDa 505 122 347 100 Dmxl2 Isoform 1 of DmX-like protein 2 IPI00853932 338 kDa 63 38 251 100 Cltc Clathrin heavy chain 1 IPI00169916 (+1) 192 kDa 1994 138 565 90 Mtap2 12 days embryo spinal cord cDNA, RIKEN full-length enriched library, clone:C530026F16 product:microtubule-associated protein 2, full insert sequenceIPI00894724 199 kDa 229 82 258 74 Mtap1a Isoform 1 of Microtubule-associated protein 1A IPI00408909 (+1) 300 kDa 310 86 214 74 Itpr1 Isoform 4 of Inositol 1,4,5-trisphosphate receptor type 1 IPI00230019 (+3) 311 kDa 37 18 155 73 Huwe1 HECT, UBA and WWE domain containing 1 IPI00463909 (+1) 483 kDa 5 5 91 69 Fasn Fatty acid synthase IPI00113223 272 kDa 24 17 140 68 Usp9x Ubiquitin carboxyl-terminal hydrolase IPI00798468 291 kDa 68 45 98 65 Lrp1 Prolow-density lipoprotein receptor-related protein 1 precursor IPI00119063 505 kDa 92 53 109 62 Myh10 Myosin-10 IPI00515398 (+1) 229 kDa 65 40 98 59 Mical1 NEDD9-interacting protein with calponin homology and LIM domains IPI00116371 117 kDa 2 2 203 57 Plec1 Isoform PLEC-1I of Plectin-1 IPI00229509 (+10) 517 kDa 121 62 110 57 Nbea Isoform 4 of Neurobeachin IPI00320836 (+1) 326 kDa 7 7 99 55 Dnm1 Isoform 3 of Dynamin-1 IPI00465648 (+1) 96 kDa 57 35 94 54 Ap2b1 Isoform 1 of AP-2 complex subunit beta-1 IPI00119689 (+1) 105 kDa 66 33 164 53 Mtap1b microtubule-associated protein 1B IPI00896700 270 kDa 314 78 159 53 Bcan brevican isoform 1 IPI00869394 96 kDa 40 11 378 50 Tnr Isoform 1 of Tenascin-R precursor IPI00227126 150 kDa 89 27 327 48 Spnb3 Adult male brain UNDEFINED_CELL_LINE cDNA, RIKEN full-length enriched library, clone:M5C1106A14 product:spectrin beta 3, full insert sequenceIPI00134344 271 kDa 239 62 152 47 Spire1 Isoform 2 of Protein spire homolog 1 IPI00420800 69 kDa 7 7 261 45 Ptprz1 protein tyrosine phosphatase, receptor type Z, polypeptide 1 IPI00627008 254 kDa 48 20 271 43 Ubr4 Isoform 1 of E3 ubiquitin-protein ligase UBR4 IPI00378681 (+3) 572 kDa 14 14 51 39 Ncan Neurocan core protein precursor IPI00135563 137 kDa 34 15 243 38 Hsp90aa1 Heat shock protein HSP 90-alpha IPI00330804 85 kDa 44 28 62 38 sp_K2C1_HUMAN IPIsp_K2C1_HUMAN 66 kDa 166 33 110 36 Ddb1 DNA damage-binding protein 1 IPI00316740 127 kDa 101 34 100 36 Hspa8 Heat shock cognate 71 kDa protein IPI00323357 71 kDa 159 41 78 35 Ank2 Adult retina cDNA, RIKEN full-length enriched library, clone:A930028N13 product:similar to Ankyrin-2, full insert sequence (Fragment)IPI00227235 131 kDa 96 29 116 34 Ap2a1 Isoform A of AP-2 complex subunit alpha-1 IPI00108780 (+1) 108 kDa 59 32 75 34 Nsf Vesicle-fusing ATPase IPI00656325 (+1) 83 kDa 39 30 48 33 sp_K1C10_HUMAN IPIsp_K1C10_HUMAN 60 kDa 105 27 76 32 Dhrs4 NADPH-dependent retinol dehydrogenase/reductase isoform 1 IPI00318750 30 kDa 10 8 182 31 Vcp Transitional endoplasmic reticulum ATPase IPI00622235 89 kDa 23 19 44 31 Hsph1 Isoform HSP105-alpha of Heat shock protein 105 kDa IPI00123802 (+2) 96 kDa 20 17 37 31 Zzef1 Isoform 2 of Zinc finger ZZ-type and EF-hand domain-containing protein 1 IPI00340123 (+1) 324 kDa 0 0 35 31 Tubb2a Tubulin beta-2A chain IPI00338039 50 kDa 773 32 419 30 Atp1a3 Sodium/potassium-transporting ATPase subunit alpha-3 IPI00122048 (+1) 112 kDa 67 24 103 30 Ubash3b Isoform 1 of Ubiquitin associated and SH3 domain-containing protein B IPI00331539 71 kDa 5 4 68 30 Atp6v1a Isoform 1 of Vacuolar ATP synthase catalytic subunit A IPI00407692 68 kDa 29 20 50 30 Tuba1b Tubulin alpha-1B chain IPI00117348 50 kDa 320 31 271 29 Cnp Isoform CNPI of 2',3'-cyclic-nucleotide 3'-phosphodiesterase IPI00229598 (+1) 45 kDa 116 24 108 29 Hk1 Hk1 protein IPI00762858 102 kDa 28 21 40 29 Nf1 Isoform 2 of Neurofibromin IPI00108783 (+1) 320 kDa 0 0 36 29 sp_K22E_HUMAN IPIsp_K22E_HUMAN 66 kDa 96 24 74 28 Dpysl2 Dihydropyrimidinase-related protein 2 IPI00114375 62 kDa 45 26 73 28 Pabpc1 Polyadenylate-binding protein 1 IPI00124287 (+1) 71 kDa 6 6 56 28 Hspa4l Isoform 1 of Heat shock 70 kDa protein 4L IPI00317710 94 kDa 21 17 41 28 Hspa9 heat shock protein 9 IPI00880839 73 kDa 68 34 40 28 Syn1 Isoform Ia of Synapsin-1 IPI00649886 74 kDa 67 26 155 27 Ncam1 Isoform N-CAM 180 of Neural cell adhesion molecule 1, 180 kDa isoform precursor IPI00122971 119 kDa 108 23 127 27 Plxnb1 Plexin-B1 precursor IPI00229992 231 kDa 3 3 70 27 Hadha Trifunctional enzyme subunit alpha, mitochondrial precursor IPI00223092 83 kDa 7 6 48 27 Nfasc Neurofascin precursor IPI00329927 138 kDa 28 18 40 27 Actg1 Actin, cytoplasmic 2 IPI00874482 42 kDa 59 20 122 26 Cyfip2 Cytoplasmic FMR1-interacting protein 2 IPI00405625 146 kDa 28 19 42 26 Hspa4 Heat shock 70 kDa protein 4 IPI00331556 94 kDa 34 25 38 26 Pi4ka Phosphatidylinositol 4-kinase, catalytic, alpha polypeptide IPI00115875 231 kDa 5 3 37 26 Htt huntingtin IPI00271166 345 kDa 0 0 34 26 Wdr7 WD repeat domain 7 IPI00380997 (+1) 163 kDa 25 19 51 25 Vps13c Chorein IPI00473340 (+3) 415 kDa 0 0 40 25 Copa Coatomer subunit alpha IPI00229834 138 kDa 14 12 29 25 Vcan versican IPI00875672 367 kDa 20 7 140 24 Hapln1 Hyaluronan and proteoglycan link protein 1 precursor IPI00131995 40 kDa 4 4 73 24 Nrxn1 Isoform 2 of Neurexin-1-alpha precursor IPI00230050 (+2) 165 kDa 0 0 63 24 Ap2a2 adaptor protein complex AP-2, alpha 2 subunit IPI00753468 104 kDa 43 20 61 24 Epb4.1l3 Isoform 1 of Band 4.1-like protein 3 IPI00125501 (+2) 103 kDa 55 28 60 24 sp_K1C9_HUMAN IPIsp_K1C9_HUMAN 62 kDa 86 23 43 24 Stxbp1 Isoform 1 of Syntaxin-binding protein 1 IPI00415402 68 kDa 36 25 39 24 Sept11 Isoform 3 of Septin-11 IPI00420385 (+2) 49 kDa 27 18 32 24 Nefm Neurofilament medium polypeptide IPI00323800 96 kDa 134 44 46 23 Cntn1 Contactin-1 precursor IPI00123058 113 kDa 5 5 40 23 Hspa5 78 kDa glucose-regulated protein precursor IPI00319992 72 kDa 59 29 39 23 Tln2 talin 2 IPI00229647 272 kDa 5 5 32 23 Trim32 Tripartite motif-containing protein 32 IPI00321005 72 kDa 8 7 29 23 Mtap6 microtubule-associated protein 6 isoform 1 IPI00115833 96 kDa 63 25 64 22 Nefh Neurofilament heavy polypeptide IPI00114241 (+1) 117 kDa 103 29 49 22 Rtn4 Isoform 1 of Reticulon-4 IPI00469392 127 kDa 56 24 46 22 Synj1 similar to mKIAA0910 protein IPI00850983 (+3) 189 kDa 18 12 44 22 L1cam L1 cell adhesion molecule IPI00785371 141 kDa 16 12 43 22 Nefl Neurofilament light polypeptide IPI00554928 62 kDa 69 26 37 22 5031439G07Rik Novel protein IPI00464302 50 kDa 0 0 34 22 Ap1b1 Adult male diencephalon cDNA, RIKEN full-length enriched library, clone:9330159F11 product:adaptor protein complex AP-1, beta 1 subunit, full insert sequenceIPI00648683 105 kDa 42 4 138 21 Syn2 Isoform IIa of Synapsin-2 IPI00469548 63 kDa 51 13 101 21 Ap2m1 AP-2 complex subunit mu-1 IPI00116356 50 kDa 32 13 72 21 Pdha1 Pyruvate dehydrogenase E1 component subunit alpha, somatic form, mitochondrial precursorIPI00337893 43 kDa 15 9 41 21 Idh3b Tumor-related protein IPI00126635 42 kDa 51 23 40 21 Sept7 cell division cycle 10 homolog IPI00224626 51 kDa 26 14 37 21 Sbf1 Putative uncharacterized protein IPI00752390 (+1) 211 kDa 2 2 26 21 Lrpprc Leucine-rich PPR motif-containing protein, mitochondrial precursor IPI00420706 157 kDa 0 0 23 21 Snap91 Isoform Long of Clathrin coat assembly protein AP180 IPI00122409 (+2) 92 kDa 46 19 48 20 Atp6v1b2 Vacuolar ATP synthase subunit B, brain isoform IPI00119113 57 kDa 11 7 29 20 Atp5b ATP synthase subunit beta, mitochondrial precursor IPI00468481 56 kDa 19 14 27 20 Cand1 TBP-interacting protein isoform 1 IPI00420562 (+1) 159 kDa 16 16 20 20 Mbp Isoform 4 of Myelin basic protein IPI00223377 22 kDa 297 17 228 19 Gcdh glutaryl-Coenzyme A dehydrogenase IPI00788331 49 kDa 0 0 44 19 Ppp2r1a Serine/threonine-protein phosphatase 2A 65 kDa regulatory subunit A alpha isoformIPI00310091 65 kDa 31 19 32 19 Dctn1 Dctn1 protein IPI00856365 140 kDa 43 31 31 19 Tcp1 Isoform 1 of T-complex protein 1 subunit alpha B IPI00459493 60 kDa 16 10 27 19 Nrcam 123 kDa protein IPI00876075 123 kDa 11 10 25 19 Atp5a1 ATP synthase subunit alpha, mitochondrial precursor IPI00130280 60 kDa 16 13 24 19 ENSMUSG00000070490;Gapdh;100041325;ENSMUSG00000072451;LOC100048291;100040053;ENSMUSG00000068459;OTTMUSG00000005227;LOC100042025;LOC100046067;OTTMUSG00000005300 Glyceraldehyde-3-phosphate dehydrogenaseIPI00273646 (+1) 36 kDa 80 15 88 18 Hsp90ab1 Heat shock protein 84b IPI00229080 83 kDa 43 12 59 18 Icam5 intercellular adhesion molecule 5, telencephalin IPI00877299 97 kDa 8 7 36 18 Hnrnpm Isoform 1 of Heterogeneous nuclear ribonucleoprotein M IPI00132443 (+1) 78 kDa 15 14 28 18 Aldoa Fructose-bisphosphate aldolase A IPI00221402 39 kDa 7 7 27 18 Cct8 T-complex protein 1 subunit theta IPI00469268 60 kDa 10 9 23 18 Gpd2 Glycerol phosphate dehydrogenase 2, mitochondrial IPI00331182 (+1) 83 kDa 0 0 22 18 Pkm2 Isoform M1 of Pyruvate kinase isozymes M1/M2 IPI00845840 58 kDa 7 5 21 18 Cadps Isoform 1 of Calcium-dependent secretion activator 1 IPI00668903 (+1) 153 kDa 6 5 21 18 Kif21a Isoform 1 of Kinesin-like protein KIF21A IPI00454081 (+4) 187 kDa 0 0 21 18 Ryr2 ryanodine receptor 2, cardiac IPI00338309 565 kDa 0 0 21 18 Ctnna2 Visual cortex cDNA, RIKEN full-length enriched library, clone:K530006G14 product:catenin alpha 2, full insert sequenceIPI00230751 102 kDa
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  • Inhibition of the MID1 Protein Complex

    Inhibition of the MID1 Protein Complex

    Matthes et al. Cell Death Discovery (2018) 4:4 DOI 10.1038/s41420-017-0003-8 Cell Death Discovery ARTICLE Open Access Inhibition of the MID1 protein complex: a novel approach targeting APP protein synthesis Frank Matthes1,MoritzM.Hettich1, Judith Schilling1, Diana Flores-Dominguez1, Nelli Blank1, Thomas Wiglenda2, Alexander Buntru2,HannaWolf1, Stephanie Weber1,InaVorberg 1, Alina Dagane2, Gunnar Dittmar2,3,ErichWanker2, Dan Ehninger1 and Sybille Krauss1 Abstract Alzheimer’s disease (AD) is characterized by two neuropathological hallmarks: senile plaques, which are composed of amyloid-β (Aβ) peptides, and neurofibrillary tangles, which are composed of hyperphosphorylated tau protein. Aβ peptides are derived from sequential proteolytic cleavage of the amyloid precursor protein (APP). In this study, we identified a so far unknown mode of regulation of APP protein synthesis involving the MID1 protein complex: MID1 binds to and regulates the translation of APP mRNA. The underlying mode of action of MID1 involves the mTOR pathway. Thus, inhibition of the MID1 complex reduces the APP protein level in cultures of primary neurons. Based on this, we used one compound that we discovered previously to interfere with the MID1 complex, metformin, for in vivo experiments. Indeed, long-term treatment with metformin decreased APP protein expression levels and consequently Aβ in an AD mouse model. Importantly, we have initiated the metformin treatment late in life, at a time-point where mice were in an already progressed state of the disease, and could observe an improved behavioral phenotype. These 1234567890 1234567890 findings together with our previous observation, showing that inhibition of the MID1 complex by metformin also decreases tau phosphorylation, make the MID1 complex a particularly interesting drug target for treating AD.
  • PNAS 07-04849-SI Table 3. 6-18-2007

    PNAS 07-04849-SI Table 3. 6-18-2007

    Table 5. β-arrestin 2-interacting proteins under nonstimulated (-) condition IPI accession Swiss- Number of Prot Gene symbol Protein name experiments accession number number detected Signal transduction Adaptor proteins IPI00027355 P32121 ARRB2 β-arrestin 2 6 IPI00293857 P49407 ARRB1 β-arrestin 1 6 IPI00021353 P10523 SAG S-arrestin (Retinal S-antigen) (48 kDa protein) (S-AG) (Rod photoreceptor arrestin) 2 IPI00003917 P36575 ARR3 X-arrestin (Arrestin-C) (Cone arrestin) (cArr) (Retinal cone arrestin-3) (C-arrestin) 2 IPI00216318 P31946 YWHAB 14-3-3 β/α (14-3-3 protein beta/alpha) (Protein kinase C inhibitor protein 1) (KCIP-1) (Protein 1054) 2 IPI00220642 P61981 YWHAG 14-3-3 γ (14-3-3 protein gamma) (Protein kinase C inhibitor protein 1) (KCIP-1) 2 IPI00018146 P27348 YWHAQ 14-3-3 θ (14-3-3 protein tau) (14-3-3 protein theta) (14-3-3 protein T-cell) (HS1 protein) 2 IPI00216319 Q04917 YWHAH 14-3-3 η (14-3-3 protein eta) (Protein AS1) 2 IPI00000816 P62258 YWHAE 14-3-3 ε (14-3-3 protein epsilon) (14-3-3E) 2 Protein kinases IPI00027251 Q15208 STK38 STK38 (Serine/threonine-protein kinase 38) (NDR1 protein kinase) (Nuclear Dbf2-related kinase 1) 4 SCY1-like 2 (SCY1-like 2 protein) (coated vesicle-associated kinase of 104 kDa) (Eukaryotic protein IPI00396218 Q6P3W7 SCYL2 2 kinase family protein) (CDNA FLJ10074 fis, clone HEMBA1001744, weakly similar to SCY1 IPI00013835 Q13574 DGKZ DGK ζ (Diacylglycerol kinase zeta) (Diglyceride kinase zeta) (DGK-zeta) (DAG kinase zeta) 2 DGK ε (Diacylglycerol kinase epsilon) (Diglyceride kinase epsilon) (DGK-epsilon)